Elderly patients have a high incidence of adverse responses to drugs, reflecting both high rate of drug utilization and single or combined drug therapy which is inappropriate for this age group. Factors which influence altered drug responses in older persons have not been adequately identified. Our research project will explore, in rats, age-related changes in: drug absorption from the intestine, intestinal motility and transit, hepatic drug metabolism, penetration of drug molecules into the brain, sensitivity of brain receptors to drug, and responsiveness of a model physiological system to drugs. Morphine will be used as the prototype drug in these studies to determine what is different as a result of age. Simultaneously, we will explore why differences occur by examination of model systems which control genetic transcription of nucleic acids and synthesis of essential proteins. A method has been developed to enhance RNA polymerase activity, which can be applied to studies of basic age-related changes in enzyme formation and activity.